The present study of human chromosome 12 loci revealed that the Ser127Gly polymorphism in PTPRB is associated with substance abuse vulnerability in three independent case-control samples (European-American from COGA families, USA, n = 177, P = 0.047; European-American from Maryland, USA, n = 650, P = 0.018; and African-American from Maryland, USA, n = 331, P = 0.009).